title: Integrated photocatalytic micropillar nanoreactor electrospray ionization chip for mimicking phase I metabolic reactions.
abstract: We developed a nanoreactor chip based system to mimic phase I metabolic reactions of small organic compounds. The microchip, made of silicon, has an anatase-phase titanium dioxide (TiO(2)) nanolayer coating for photocatalysis and an integrated electrospray ionization (ESI) tip for direct mass spectrometric (MS) analysis. This novel method for mimicking phase I metabolic reactions uses an on-chip TiO(2)-nanolayer and an external UV-lamp to induce photocatalyzed chemical reactions of drug compounds in aqueous solutions. The reactions of selected test compounds (verapamil, metoprolol, propranolol, lidocaine, 2-acetamidofluorene, and S-methylthiopurine) produced mostly the same main products as phase I metabolic reactions induced by human liver microsomes, rat hepatocytes, or cytochrome P enzymes, showing hydroxylation, dehydrogenation, and dealkylations as the main photocatalytic reactions. With this method it is possible to detect reactive and toxic products (mimicking reactive metabolites) due to the absence of biological matrices and an immediate analysis. The method used is sensitive: only 20-40 pmol (1-10 ng) of a substrate was needed for the experiment, thus it provides an inexpensive method for screening possible metabolites of new drug candidates. Due to small dimensions of the microchip, diffusion lengths are suitable for the high reaction rates, thus providing a rapid analysis as the reaction products can be detected and identified directly after the photoinduced reactions have occurred. The method shows a similar performance to that of electrochemistry, a commonly used technique for mimicking phase I metabolism.
authors.affiliation: Division of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
authors.forename: Teemu
authors.initials: T
authors.lastname: Nissilä
authors.forename: Lauri
authors.initials: L
authors.lastname: Sainiemi
authors.forename: Mika-Matti
authors.initials: MM
authors.lastname: Karikko
authors.forename: Marianna
authors.initials: M
authors.lastname: Kemell
authors.forename: Mikko
authors.initials: M
authors.lastname: Ritala
authors.forename: Sami
authors.initials: S
authors.lastname: Franssila
authors.forename: Risto
authors.initials: R
authors.lastname: Kostiainen
authors.forename: Raimo A
authors.initials: RA
authors.lastname: Ketola
mesh_terms: D000818:Animals; D032701:Biomimetics / Q000295:instrumentation*; D002384:Catalysis; D004563:Electrochemistry; D005240:Feasibility Studies; D006801:Humans; D056656:Lab-On-A-Chip Devices; D050216:Metabolic Detoxication, Phase I; D008970:Molecular Weight; D036103:Nanotechnology / Q000295:instrumentation*; D009930:Organic Chemicals / Q000737:chemistry / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism; D055668:Photochemical Processes; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization / Q000295:instrumentation*; D018511:Systems Integration; D014025:Titanium / Q000737:chemistry
chemical_list: D009930:Organic Chemicals; D004364:Pharmaceutical Preparations; C009495:titanium dioxide; D014025:Titanium